Sex and adrenal hormones in association with insecticide biomarkers among adolescents living in ecuadorian agricultural communities.

BACKGROUND: Organophosphate, pyrethroid, and neonicotinoid insecticides have resulted in adrenal and gonadal hormone disruption in animal and in vitro studies; limited epidemiologic evidence exists in humans. We assessed relationships of urinary insecticide metabolite concentrations with adrenal and gonadal hormones in adolescents living in Ecuadorean agricultural communities. METHODS: In 2016, we examined 522 Ecuadorian adolescents (11-17y, 50.7% female, 22% Indigenous; ESPINA study). We measured urinary insecticide metabolites, blood acetylcholinesterase activity (AChE), and salivary testosterone, dehydroepiandrosterone (DHEA), 17ß-estradiol, and cortisol. We used general linear models to assess linear (ß = % hormone difference per 50% increase of metabolite concentration) and curvilinear relationships (ß2 = hormone difference per unit increase in squared ln-metabolite) between ln-metabolite or AChE and ln-hormone concentrations, stratified by sex, adjusting for anthropometric, demographic, and awakening response variables. Bayesian Kernel Machine Regression was used to assess non-linear associations and interactions. RESULTS: The organophosphate metabolite malathion dicarboxylic acid (MDA) had positive associations with testosterone (ßboys = 5.88% [1.21%, 10.78%], ßgirls = 4.10% [-0.02%, 8.39%]), and cortisol (ßboys = 6.06 [-0.23%, 12.75%]. Para-nitrophenol (organophosphate) had negatively-trending curvilinear associations, with testosterone (ß2boys = -0.17 (-0.33, -0.003), p = 0.04) and DHEA (ß2boys = -0.49 (-0.80, -0.19), p = 0.001) in boys. The neonicotinoid summary score (ßboys = 5.60% [0.14%, 11.36%]) and the neonicotinoid acetamiprid-N-desmethyl (ßboys = 3.90% [1.28%, 6.58%]) were positively associated with 17ß-estradiol, measured in boys only. No associations between the pyrethroid 3-phenoxybenzoic acid and hormones were observed. In girls, bivariate response associations identified interactions of MDA, Para-nitrophenol, and 3,5,6-trichloro-2-pyridinol (organophosphates) with testosterone and DHEA concentrations. In boys, we observed an interaction of MDA and Para-nitrophenol with DHEA. No associations were identified for AChE. CONCLUSIONS: We observed evidence of endocrine disruption for specific organophosphate and neonicotinoid metabolite exposures in adolescents. Urinary organophosphate metabolites were associated with testosterone and DHEA concentrations, with stronger associations in boys than girls. Urinary neonicotinoids were positively associated with 17ß-estradiol. Longitudinal repeat-measures analyses would be beneficial for causal inference.

Urinary Glyphosate, 2,4-D and DEET Biomarkers in Relation to Neurobehavioral Performance in Ecuadorian Adolescents in the ESPINA Cohort.

BACKGROUND: Herbicides are the most used class of pesticides worldwide, and insect repellents are widely used globally. Yet, there is a dearth of studies characterizing the associations between these chemical groups and human neurobehavior. Experimental studies suggest that glyphosate and 2,4-dichlorophenoxyacetic acid (2,4-D) herbicides can affect neurobehavior and the cholinergic and glutamatergic pathways in the brain. We aim to assess whether herbicides and insect repellents are associated with neurobehavioral performance in adolescents. METHODS: We assessed 519 participants (11-17 years of age) living in agricultural communities in Ecuador. We quantified urinary concentrations of glyphosate, 2,4-D, and two N,N-diethyl-meta-toluamide (DEET) insect repellent metabolites [3-(diethylcarbamoyl)benzoic acid (DCBA) and 3-(ethylcarbamoyl)benzoic acid (ECBA)] using isotope-dilution mass spectrometry. We assessed neurobehavioral performance using 9 subtests across 5 domains (attention/inhibitory control, memory/learning, language, visuospatial processing, and social perception). We characterized the associations using generalized estimating equations and multiple imputation for metabolites below detection limits. Models were adjusted for demographic and anthropometric characteristics, urinary creatinine, and sexual maturation. Mediation by salivary cortisol, dehydroepiandrosterone, 17ß-estradiol, and testosterone was assessed using structural equation modeling. RESULTS: The mean of each neurobehavioral domain score was between 7.0 and 8.7 [standard deviation (SD) range: 2.0-2.3]. Glyphosate was detected in 98.3% of participants, 2,4-D in 66.2%, DCBA in 63.3%, and ECBA in 33.4%. 2,4-D was negatively associated with all neurobehavioral domains, but statistically significant associations were observed with attention/inhibition [score difference per 50% higher metabolite concentration (ß)=-0.19 95% confidence interval (CI): -0.31, -0.07], language [ß=-0.12 (95% CI: -0.23, -0.01)], and memory/learning [ß=-0.11 (95% CI: -0.22, 0.01)]. Glyphosate had a statistically significant negative association only with social perception [ß=-0.08 (95% CI: -0.14, -0.01)]. DEET metabolites were not associated with neurobehavioral performance. Mediation by gender and adrenal hormones was not observed. CONCLUSION: This study describes worse neurobehavioral performance associated with herbicide exposures in adolescents, particularly with 2,4-D. Replication of these findings among other pediatric and adult populations is needed. https://doi.org/10.1289/EHP11383.

A Neighborhood-level analysis of mental health distress and income inequality as quasi-longitudinal risk of reported COVID-19 infection and mortality outcomes in Chicago.

Extant literature investigates the impact of COVID-19 on mental health outcomes, however there is a paucity of work examining mental health distress as a risk factor for COVID-19 outcomes. While systemic variables like income inequality relate to both mental health and COVID-19, more work is needed to test theoretically informed models including such variables. Using a social-ecological framework, we aimed to address these gaps in the literature by conducting a neighborhood-level analysis of potential mental health distress and systemic- (income inequality) level predictors of reported COVID-19 infection and mortality over time in Chicago. Neighborhood-level comparisons revealed differences in mental health distress, income inequality, and reported COVID-19 mortality, but not reported COVID-19 infection. Specifically, Westside and Southside neighborhoods generally reported higher levels of mental health distress and greater concentration of poverty. The Central neighborhood showed a decline in reported mortality rates over time. Multi-level negative binomial models established that Zip-codes with greater mental health distress were at increased reported COVID-19 infection risk, yet lower mortality risk; Zip-codes with more poverty were at increased reported COVID-19 infection risk, yet lower mortality risk; and Zip-codes with the highest percentage of People of Color were at decreased risk of reported COVID-19 mortality. Taken together, these findings substantiate Chicago neighborhood-level disparities in mental health distress, income inequality, and reported COVID-19 mortality; identify unique differential associations of mental health distress and income inequality to reported COVID-19 infection and reported mortality risk; and, offer an alternative lens towards understanding COVID-19 outcomes in terms of race/ethnicity.

Impact of timing of multimodal analgesia in enhanced recovery after cesarean delivery protocols on postoperative opioids: A single center before-and-after study.

STUDY OBJECTIVE: Enhanced recovery after cesarean delivery (ERAC) programs aim to decrease maternal morbidity and aid in maternal recovery and return to baseline. Multimodal analgesia is an important element of ERAC protocols, but no consensus exists on the timing of medication administration. We compared maternal pain outcomes following scheduled cesarean delivery with modification of the timing of administration of multimodal analgesia with non-steroidal anti-inflammatory drugs (NSAIDs) and acetaminophen. DESIGN: Before-and-after study. SETTING: Labor and delivery unit at a single academic institution. INTERVENTION: NSAIDs and acetaminophen were administered as a fixed-interval alternating regimen every 3 h for the initial ERAC group (ERAC 1) and fixed-interval combined regimen every 6 h for the modified ERAC group (ERAC 2). ERAC 1 and ERAC 2 groups were compared to historical controls (Pre-ERAC). PATIENTS: 520 women undergoing scheduled cesarean delivery (Pre-ERAC n = 179, ERAC 1 n = 179, and ERAC 2 n = 162). MEASUREMENTS: The primary outcomes were postoperative total and daily opioid utilization as measured in morphine milligram equivalents (MME). Secondary outcomes included postoperative length of stay, maximum pain scores, and racial disparities in care. MAIN RESULTS: The modified schedule of non-opioid analgesics involving combined administration (ERAC 2) versus alternating administration (ERAC 1) of multimodal analgesia resulted in decreased total postoperative opioid utilization (median = 26.3 vs 52.5 MME, Bonferroni corrected P = 0.002). Total postoperative opioid utilization among the ERAC 2 group was also significantly reduced compared to the Pre-ERAC group (median = 26.3 vs 105.0 MME, Bonferroni corrected P < 0.0001). CONCLUSIONS: Multidisciplinary teams developing or modifying ERAC protocols for scheduled cesarean delivery should consider a combined administration at fixed intervals of NSAIDs and acetaminophen throughout the hospital stay to optimize postoperative pain management.

Dietary Acid Load, Serum Polychlorinated Biphenyl Levels, and Mortality Following Breast Cancer in the Long Island Breast Cancer Study Project.

Dietary acid load (DAL) may be associated with all-cause mortality (ACM) and breast cancer-specific mortality (BCM), and these associations may be modified by serum polychlorinated biphenyl (PCB) levels. Participants included 519 women diagnosed with first primary in situ or invasive breast cancer in 1996/1997 with available lipid-corrected PCB data. After a median of 17 years, there were 217 deaths (73 BCM). Potential renal acid load (PRAL) and net endogenous acid production (NEAP) scores calculated from a baseline food frequency questionnaire estimated DAL. Cox regression estimated covariate-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between PRAL and NEAP with mortality. We evaluated effect measure modification by total serum PCB levels (>median vs. ≤median). PRAL quartile 4 versus quartile 1 was associated with an ACM HR of 1.31 (95%CI = 0.90-1.92). In the upper median of PCBs, ACM HRs were 1.43 (95%CI = 0.96-2.11) and 1.40 (95%CI = 0.94-2.07) for PRAL and NEAP upper medians, respectively. In the lower median of PCBs, the upper median of NEAP was inversely associated with BCM (HR = 0.40, 95%CI = 0.19-0.85). DAL may be associated with increased risk of all-cause mortality following breast cancer among women with high total serum PCB levels, but inversely associated with breast cancer mortality among women with low PCB levels.